The main objective of the project is to search for unrecognized bladder carcinogens in the human environment. Drugs, food additives, and industrial compounds are being considered. The metabolism of suspect chemicals will be examined in human urine to determine whether carcinogenic N-hydroxy metabolites are formed. Gas chromatography, utilizing the electron capture detector, HPLC and GC-mass spectrometry will be the primary analytical methods used. Compounds being studied include caffeine, theobromine, theophylline, sulfadiazine, p-aminosalicylic acid, ampicillin, phenacetin, acetaminophen and acetanilid. Industrial amines being evaluated in dogs are methylenedianiline, 4,4'-methylene-bis (2-chloroaniline) dichlorobenzidine, 2,2-bis(p-amino-phenyl) and 4,4'-methylene-bis-(2-methylaniline). Previous results show that dimethylnitrosamine is formed in the bladder during urinary tract infection. If this is an etiological factor in bladder cancer, it must be shown that the DMN can be activated by and react with bladder mucosa. Experiments to demonstrate this are under way. Experiments to demonstrate the importance of the induction of hyperplasia by the naphthylamines and the inhibitions of this effect by retinoic acid will be carried out. The anticarcinogenic effect of 1-naphthylamine against 2-naphthylamine will be investigated. The project will be carried out in conjunction with the Urology clinic of the University of Miami, School of Medicine which sees approximately 100 bladder cancer patients annually.